Antisense Oligonucleotides
Antisense Oligonucleotides (ASOs) usually refer to short, synthetic, single-stranded DNA or RNA (13-30 nucleotides). Following binding to the targeted mRNA or pre-mRNA, ASOs modulates RNA function by several different mechanisms.
1. ASOs can form an RNA–DNA hybrid that becomes a substrate for RNase H, resulting in target mRNA degradation.
2. ASOs can modulate gene expression via steric block of the ribosomal machinery, which can lead to reduced expression, modulation of splicing and/or restoration of a functional protein.
3. Binding of ASOs to pre-mRNA can alter splicing factor recruitment and regulate splicing events.
The first in vivo applications of ASOs showed limited clinical potential because of the high susceptibility of ASOs with an unmodified phosphoribose backbone to rapid degradation by endonucleases and exonucleases. The modifications in backbone, and sugar molecules give ASOs more affinity and stability. Phosphorodiamidate morpholino oligomers (PMO) are very resistant to nuclease and protease degradation and are mostly used in splicing modulation or translation inhibition. Chemical modifications at 2' position of ribose sugar ring such as 2’-O-methyl (2’-O-me), 2’-Fluoro (2’-F), 2’-O-methoxyethyl (2’-MOE) allow oligonucleotide to adopt RNA like C3’-endo sugar pucker, making it thermally stable.
- Formula: C177H226N63O89P15S15
- Molecular Weight: 5605.63
Frenlosirsen (ION-935918; ION251) is an antisense oligonucleotide and also an IRF4 inhibitor. Frenlosirsen inhibits the survival of malignant plasma cells, reduces the burden of myeloma progenitor cells and prevents disease recurrence. Frenlosirsen is applicable to myeloma-related research.
- Molecular Weight: 7283.90
ISIS 104838 is an antisense oligonucleotide targeting TNF-α. ISIS 104838 specifically binds to human TNF-α mRNA via Watson-Crick base pairing to form a DNA:RNA hybrid duplex, thereby recruiting the ubiquitously expressed intracellular enzyme RNase H to degrade the target mRNA and inhibit TNF-α protein synthesis at the transcriptional level. ISIS 104838 induces moderate, self-limiting thrombocytopenia in cynomolgus monkeys. ISIS 104838 can be used for the study of inflammatory diseases.
- Molecular Weight: 7165.06 (free acid)
Volanesorsen scramble negative control is a negative control for volanesorsen (HY-145727) with the sequence: CAUGUTCUTCUGCATGUCAU. Volanesorsen (ISIS 304801) is an antisense oligonucleotide inhibitor of apolipoprotein CIII (apo-CIII) mRNA that can lower triglyceride levels and improve insulin resistance.
- Molecular Weight: 6920.84 (free acid)
- Molecular Weight: 7309.194 (free acid)
IONIS-GCCRRx (ISIS 426115) sodium, a glucocorticoid receptor antagonist, is a 2'-O-methoxyethyl (2'-MOE) antisense oligonucleotide (ASO).
- Molecular Weight: 5290.25 (free acid)
EZN-2968 sodium is an antisense oligonucleotide that specifically binds and inhibits the expression of HIF-1α mRNA. EZN-2968 sodium, inhibits tumor cell growth.
- Molecular Weight: 8636.00
Pelacarsen (ISIS 681257) is a GalNAc3-conjugated 2′-MOE-modified antisense oligonucleotide. Pelacarsen reduces apo (a).
- Molecular Weight: 6617.00
Rovanersen (WVE-120101) is an antisense oligonucleotide that specifically targets mutated mRNA copies of the huntington (HTT) gene without affecting healthy mRNA of HTT gene, thereby preventing the production of faulty Huntingtin protein. Rovanersen can be used for huntington’s disease research.
- Formula: C202H240N82Na19O111P19S13
- Molecular Weight: 6617 (free acid)
Rovanersen sodium is an antisense oligonucleotide that specifically targets mutated mRNA copies of the huntington (HTT) gene without affecting healthy mRNA of HTT gene, thereby preventing the production of faulty Huntingtin protein. Rovanersen sodium can be used for huntington’s disease research.
- Formula: C230H301N67O127P19S13Na19
- Molecular Weight: 7060.8 (free acid)
Zilganersen (ION373) sodium is a gapmer antisense oligonucleotide targeting glial fibrillary acidic protein (GFAP). Zilganersen sodium reduces excess glial fibrillary acidic protein produced by disease-causing variants in the GFAP gene and inhibits synthesis of GFAP. Zilganersen sodium can be used for the research of Alexander disease.
Vupanorsen is an N-acetyl galactosamine-conjugated antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. Vupanorsen lowers triglycerides and atherogenic lipoproteins.
- Molecular Weight: 4736.00
Cobomarsen (MRG-106) is an oligonucleotide inhibitor of miR-155. Cobomarsen inhibits multiple gene pathways associated with cell survival (including JAK/STAT, MAPK/ERK and PI3K/AKT). Cobomarsen can be used for the research of B-cell lymphoma.
- Molecular Weight: 4967.00
gDIS3-13 is an antisense oligonucleotide targeting the DIS3 gene. gDIS3-13 can reduce cell growth and increase apoptosis in multiple myeloma (MM).
- Formula: C273H391N81O144P20S20
- Molecular Weight: 8372.24
Ultevursen (QR-421a) is a splice-modulating antisense oligonucleotide targeting exon 13 of the USH2A gene, which restores the functional expression of Usherin protein by inducing exon skipping. Ultevursen binds to USH2A pre-mRNA and modulates the splicing process to specifically skip exon 13 carrying the pathogenic mutation c.2299delG, generating an in-frame transcript and a truncated yet functionally normal protein. Ultevursen exhibits concentration-dependent exon skipping activity in human cells and retinal organoid models, and restores Usherin expression and retinal function in zebrafish and gene-edited mouse models. Ultevursen can be used for related research on type 2 Usher syndrome and non-syndromic retinitis pigmentosa.
- Formula: C273H370N81Na21O144P20S20
- Molecular Weight: 8372.24 (free acid)
Ultevursen sodium (QR-421a) is a splice-modulating antisense oligonucleotide targeting exon 13 of the USH2A gene, which restores the functional expression of Usherin protein by inducing exon skipping. Ultevursen sodium binds to USH2A pre-mRNA and modulates the splicing process to specifically skip exon 13 carrying the pathogenic mutation c.2299delG, generating an in-frame transcript and a truncated yet functionally normal protein. Ultevursen sodium exhibits concentration-dependent exon skipping activity in human cells and retinal organoid models, and restores Usherin expression and retinal function in zebrafish and gene-edited mouse models. Ultevursen sodium can be used for related research on type 2 Usher syndrome and non-syndromic retinitis pigmentosa.
- Molecular Weight: 7584.00
Casimersen (SRP-4045) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass. Casimersen binds to exon 45 of dystrophin pre-mRNA, restores the open-reading frame (by skipping exon 45) resulting in the production of an internally truncated but functional dystrophin protein. Casimersen can be used for the research of Duchenne muscular dystrophy (DMD).
Mipomersen sodium scrambled negative control is the sequence scrambled negative control of Mipomersen sodium.
- Molecular Weight: 7666.10
FAM labled Nusinersen sodiumis a FAM labled Nusinersen sodium.
